JAC-Antimicrobial Resistance最新文献

Background: Pathogens causing neonatal sepsis have developed resistance to antimicrobial treatment, resulting in the convergence of two public health issues; neonatal mortality and antimicrobial resistance. There are a few published studies presenting data from South Africa regarding neonatal sepsis pathogen and resistance profiles.

Methods: We conducted a systematic review of bacterial and fungal neonatal sepsis pathogens and antimicrobial resistance profiles from 2005 to 2022.

Results: Nine studies were included from 1235 screened. Most studies were from two provinces in South Africa and were conducted at academic hospitals. A single study included data collected nationally. Significant heterogeneity was noted, precluding the value of conducting a formal meta-analysis. There was significant variability in prevalence of pathogens, dependent on whether studies included coagulase negative Staphylococci (CoNS) or not. Studies that included CoNs reported higher prevalence for Gram-positive organisms compared with Gram-negative organisms versus studies that did not include CoNS. A higher proportion of Gram negatives compared with Gram positives and fungi was noted. Consistently low susceptibility to WHO first line empiric therapy was reported in most studies and low susceptibility to second line therapy reported in some studies. Seven studies reported mortality, which ranged from 15.6% to 46.3%.

Conclusion: The prevalence of pathogens causing neonatal sepsis in South Africa are consistent with those on the WHO list of priority bacterial and fungal pathogens. A high percentage resistance to WHO first and second line treatment is noted and emphasizes the importance of country specific surveillance for neonatal sepsis.

Objectives: To evaluate the synergistic activity of ampicillin/sulbactam plus ceftazidime/avibactam in a collection of carbapenem-resistant Acinetobacter baumannii (CR-Ab) from different regions in Peru.

Materials and methods: One hundred and eighty-four CR-Ab isolates were included in this study. They were identified by amplification of bla _OXA-51 and confirmed by MALDI-TOF (matrix-assisted laser desorption ionization time of flight) mass spectrometry and 16S rRNA sequencing. Susceptibility to ampicillin/sulbactam and carbapenems was determined by the disc diffusion method. Synergy was assessed using discs containing ampicillin/sulbactam and ceftazidime/avibactam. The EDTA-disc synergy test was used to screen metallo-β-lactamase-producing isolates, and in isolates showing synergy, the presence of bla _NDM was confirmed by PCR. Statistical analysis was performed using Fisher's exact test.

Results: High levels of resistance to ampicillin/sulbactam were found in the study. Thus, 1.1% (2/184), 11.4% (21/184) and 87.5% (161/184) of isolates were classified as susceptible, intermediate and resistant to ampicillin/sulbactam, respectively. Synergistic activity was observed in 97.2% of the non-susceptible CR-Ab isolates. The presence of metallo-β-lactamase producers (all bla _NDM) was observed in three isolates (1.6%).

Conclusions: These findings demonstrate high levels of synergistic activity between ampicillin/sulbactam and ceftazidime/avibactam and their potential use as a treatment for CR-Ab.

We describe here how we guide and work with over 100 secondary- and tertiary-care hospitals in Thailand to support the effective use of their antimicrobial resistance (AMR) surveillance data for local actions, and with policy makers for national actions. At the facility level, the guidance includes: (i) validating data, (ii) comparing data with previous reports, (iii) comparing data with other hospitals with similar levels of care and bed count, (iv) comparing cluster signals with infection prevention control records, and (v) identifying wards with hyperendemic hospital-origin AMR infections. At the national level, the guidance includes monitoring national estimates, systematically benchmarking hospital-level estimates, and developing national guidelines for empirical antimicrobial therapy. We encourage hospitals and policy makers in other low- and middle-income countries to explore, adopt and adapt this guidance, ensuring their AMR surveillance data are effectively used for their local and national actions based on their context and constraints.

Background: Rapid and accurate antimicrobial susceptibility testing (AST) is essential for managing Gram-negative bacteraemia. However, a major limitation of conventional phenotypic AST is its slow turnaround time, delaying targeted therapy.

Objectives: To evaluate the performance and turnaround time of direct-from-blood culture AST using an automated phenotypic system in paediatric patients with Gram-negative rod bacteraemia.

Methods: We retrospectively reviewed 135 positive blood cultures with Gram-negative rods from a tertiary paediatric hospital between January 2021 and December 2023. Blood cultures that yielded polymicrobial organisms were excluded from the study. Direct AST was performed by preparing bacterial suspensions directly from positive blood culture broth and analyzed using an automated phenotypic AST system (BD Phoenix^™ M50). Conventional AST from isolated colonies served as the reference. Essential agreement (EA), categorical agreement (CA), and error rates [very major error (VME), major error (ME), minor error (mE)] were assessed. Time to AST result was compared between methods.

Results: The direct AST method reduced the median turnaround time by 24.0 h compared with conventional AST (P < 0.0001). Overall EA and CA were 99.5% and 99.6%, respectively. No VMEs were observed. ME and mE rates were low at 0.25% and 0.25%, respectively, with discrepancies tending to indicate greater resistance by direct AST.

Conclusions: Direct-from-blood culture AST using an automated phenotypic system provides rapid, accurate susceptibility results in paediatric Gram-negative bacteraemia. This approach enables earlier reporting and may improve clinical outcomes and antimicrobial stewardship without additional resource burden.

Antimicrobial resistance (AMR) is a global health challenge that disproportionately affects countries and regions with limited resources. Current efforts to address AMR largely emphasize antimicrobial stewardship (AMS), community engagement and scientific research, while often overlooking systemic factors such as corruption, poverty and inflation, which significantly influence the capacity of individuals and communities to respond effectively. In this article, we suggest that AMR responses must extend beyond traditional AMS and community engagement to adopt a genuinely people-centred approach-one that empowers individuals not only to achieve optimal health but also to navigate broader social and economic constraints. To our knowledge, this is the first report to critically examine the combined impact of corruption, poverty and inflation on AMR.

Objectives: To compare the adverse event rates between daptomycin and vancomycin in the outpatient parenteral antimicrobial therapy (OPAT) setting.

Methods: This was a retrospective cohort study of patients treated with vancomycin or daptomycin in OPAT. Demographic and clinical data were abstracted from the electronic medical record. Vancomycin was dosed using Bayesian kinetics software to achieve a goal AUC of 400-600 mg h/L and daptomycin was a weight-based dose. The primary outcome was the occurrence of an adverse event resulting in a change in antimicrobial therapy or early discontinuation due to harm or injury. Secondary outcomes included measurement of time to adverse event occurrence and time in therapeutic range for the vancomycin group. The primary outcome was analyzed using a chi-square test.

Results: A total of 175 patients were included, with 112 in the daptomycin group and 63 in the vancomycin group. The primary outcome of early discontinuation of OPAT therapy was not statistically different between the daptomycin and vancomycin groups [15/112 (13%) versus 9/63 (14%); P = 0.87]. The daptomycin group demonstrated a shorter median time to adverse event occurrence compared with the vancomycin group (12 versus 30 days).

Conclusions: When comparing the rate of early discontinuation between daptomycin and vancomycin in OPAT, there was no significant difference between groups. These findings suggest that either agent may be considered in the OPAT setting depending on patient-specific factors. Dosing of vancomycin using Bayesian model dosing software may have led to a reduction of adverse events in the vancomycin group.

Background: Bacteriophage therapy offers an alternative way to counter the menace of increasing antimicrobial resistance. Despite its use in clinical practice for many decades the basic tools to study the translational pharmacodynamics of phages are not available and it is recognized that lack of understanding of phage pharmacokinetics/pharmacodynamics (PK/PD) is a severe limitation in individual patient use and clinical trial design.

Methods: Traditional in vitro PK/PD evaluation tools were used to assess the antibacterial effect of single exposures of a bacteriophage cocktail against four strains of Escherichia coli with potentially different patterns of response to phage. Initially, time-kill curves (TKCs) were performed over 48 h and subsequently a dilutional in vitro model (IVM) was used to assess the antibacterial effects over 72 h.

Results: In TKCs, the four E. coli strains showed different patterns of kill and regrowth when exposed to phage, with two strains showing a sustained drop in bacterial viable count and two showing initial kill and regrowth. Using the IVM similar bacterial PD patterns were observed, and phage titre increased inversely and consistently with E. coli kill.

Conclusions: An in vitro dilutional model can be used to study the antibacterial effect of a phage cocktail on E. coli showing strain-to-strain variation in bacterial killing and bacteriophage titre. Such models can be used to provide more nuanced information on phage PK/PD and translationally useful information for dosing in humans.

Objectives: To establish a regional expert consensus on off-label indications for recently approved antimicrobials, based on a structured Delphi methodology, to support antimicrobial stewardship programs (ASPs) in Andalusia, Spain.

Methods: As part of the NEW_SAFE project, a modified Delphi process was employed involving 32 experts in Infectious Diseases and Intensive Care from 14 Andalusian hospitals. The process comprised three survey rounds evaluating off-label uses of eight drugs: ceftazidime-avibactam, ceftolozane-tazobactam, cefiderocol, ceftaroline, ceftobiprole, dalbavancin, tedizolid, and isavuconazole. Clinical scenarios were assessed under predefined conditions (efficacy/safety, ecological impact, and cost) and circumstances (empirical versus targeted use, resistance prevalence, PK/PD advantage).

Results: The expert panel reached positive consensus (≥80% agreement) on specific off-label targeted uses for all drugs except ceftobiprole. Empirical use was generally discouraged except under clear PK/PD advantages or resistance profiles without alternatives. Notably, dalbavancin, ceftaroline, and ceftazidime-avibactam received multiple targeted-use endorsements, particularly for endocarditis, osteoarticular infections, and bacteraemia. Isavuconazole was recommended for rare fungal infections and in cases where it offers pharmacological advantages.

Conclusions: This consensus supports the judicious off-label use of new antimicrobials in specific clinical scenarios where therapeutic gaps exist. The guidance prioritizes targeted treatment over empirical use, aligning with international ASP principles and WHO recommendations. These results provide a regional reference to optimize ASP initiatives focus on new antibiotic use while minimizing ecological impact and resistance development.

Background: Intracranial infections caused by carbapenem-resistant Klebsiella pneumoniae (CRKP) pose significant therapeutic challenges, primarily due to the limited penetration of antimicrobial agents across the blood-brain barrier. Ceftazidime/avibactam demonstrates efficacy against multidrug-resistant Gram-negative pathogens. However, its CSF pharmacokinetics and optimal dosing in patients with augmented renal clearance (ARC; CrCl > 130 mL/min/1.73 m²) remain inadequately characterized.

Methods: We utilized validated high-performance liquid chromatography to quantify ceftazidime/avibactam concentrations in paired plasma and CSF samples obtained from a traumatic brain injury patient with CRKP ventriculitis and ARC (CrCl 154.37 mL/min/1.73 m²). The MIC of ceftazidime/avibactam was determined using broth microdilution in accordance with Clinical and Laboratory Standards Institute guidelines.

Results: Standard Ceftazidime/avibactam dosing (2.5 g q8h) resulted in subtherapeutic trough concentrations in both plasma (ceftazidime/avibactam: 10.39/0.96 µg/mL) and CSF (ceftazidime/avibactam: 20.4/0.68 µg/mL) against the target pathogen (MIC = 4 mg/L). Dose intensification to 2.5 g q6h administered via 3-h prolonged infusion achieved supra-therapeutic exposures (troughs: plasma 65.60/8.70 µg/mL; CSF 58.90/10.82 µg/mL; CSF/plasma ratio = 0.9 for ceftazidime), which correlated with CSF sterilization and resolution of inflammatory markers.

Conclusion: This first-in-human pharmacokinetic evidence in a patient with ARC underscores the inadequacy of conventional ceftazidime/avibactam regimens in this population. Our findings advocate for therapeutic drug monitoring-guided dose optimization incorporating extended infusions to achieve therapeutic targets. These results emphasize the critical need for personalized dosing algorithms in the neurocritical care setting.

Background: Antimicrobial resistance (AMR) poses a global health threat requiring effective education for future prescribers. Despite its urgency, there is limited evidence about how future prescribers are educated to mitigate AMR.

Objectives: To investigate associations between AMR knowledge and (i) preferred teaching methods, (ii) self-reported competency, and (iii) recall of AMR-related curricular content among Norwegian medical and veterinary students.

Methods: A cross-sectional survey of 110 students (61 medical, 49 veterinary) from two Norwegian universities assessed knowledge, preferred teaching methods, self-reported competency and self-reported curricular coverage. Bivariate analyses and multivariable linear regression identified associations with knowledge.

Results: Formal lectures, guidelines, lab-based teaching and bedside teaching were the most preferred learning methods. Students reported that lab-based teaching had contributed to their learning about AMR, scoring higher on AMR knowledge (β = 0.89, P = 0.02), whereas those confident in knowing when to transition from IV to oral antibiotics had lower knowledge scores (β = -0.86, P = 0.031). Students reported lowest competency in antifungal-related topics.

Conclusions: The findings highlight a disconnect, where confidence does not equate to knowledge, and exposure to the curriculum alone is insufficient to ensure clinical competence. AMR knowledge is associated with perceptions about lab-based learning, and misplaced confidence in specific skills. Antifungal-related topics require more attention in curricula.